Teacher Information

The Drug Connection: Design-O-Synapse

Margaret M. Russell

Overview

Projects that involve making models have always been a good way to maximize learning especially for complex concepts. The following activity uses a strategy from Problem-Based-Learning called the "ill-structured problem". It begins with a brief review of the action of neurotransmitters on synaptic transmission and is followed with building a model as an application of the effect of toxins on neurotransmission. This activity easily leads into discussion or research on the action of poisons and drugs on neurons. Extension ideas are included.

Biological Concepts

Class Time

This activity will require approximately 3 class periods (@ 60 minutes): one-half for the

review; one and one-half for the modeling activity; and one for presentations and evaluation. If you use it as a way to teach neurotransmitters allow probably 4 classes.

Background information

As early as 1905 it was conceived that some substances like drugs and hormones affected neurons through a receptor system. The action of certain drugs could mimic known biological responses and others could inhibit them. In the last decade, the horizon of known neurotransmitter-receptor interactions has exploded becoming an integral basis for understanding all biological systems. For teenagers, their own body is the most important biological system to study, and of paramount importance for them is the understanding of drug-nervous system interaction. All metabolic reactions and action potentials tend toward equilibrium so when homeostasis is disrupted untoward responses happen -even in the nervous system. The content of transmitter-receptor knowledge has become overwhelmingly specific and chemically detailed; none-the-less, high school students need to understand that the continuity of human body functions is based upon this balanced complex of neuronal processes. The purpose of this activity is to review cholinergic and biogenic amine systems of transmission and to describe where and how disruptions or modulations in these systems can happen due to poisonous or harmful substances. The action of Cyanobacterial toxins at synapses will be used as a model for learning some of these drug-neuron interactions.

Materials

Teacher Preparation

• The Ill-structured problem strategy: A problem is posed in such a way as to allow

students to learn how to narrow the problem by repeatedly asking more and more focused

questions until a solution is possible or an action can be taken. A context(real life scenario) and a task are given with few details. The students brainstorm in their teams what it is they need to know; pose the questions; and continue using problem solving strategies until they come up with the answers or solutions needed. Resources in this activity will include the teacher, the article, some Web sites and any other neuropharmacology sources you can

Teacher Information

supply. These will provide clues, data, and direction for student work. Their goal as a team is

to learn the concepts necessary to solve the problem, use good problem solving strategies and

produce a product.

• Develop a creative way to heighten their curiosity and interest as you introduce the task given to them as specialists in neuropharmacology by the World Health Organization.

Decide on a way to divide students into teams and on the roles they are to take, i.e., Chief Researcher, Scientific Illustrator, Materials Manager, etc.

• Key resource: Read the article "The Toxins of Cyanobacteria" by Wayne W. Carmichael in Scientific American, January 1994, pp. 78-86. I also recommend reading chapter 44 in Biology , written by Campbell. (For extensions you may also want to read "Brain By Design" by Richard Restak, in The Sciences, September/October 1993 pp. 27-33.)

• Prepare a review including the following:

Vocabulary: synapse; vesicle; neurotransmitter; presynaptic membrane; postsynaptic membrane; excitatory potential and depolarization; inhibitory potential and hyperpolar-ization; voltage gated channels; ligand gated channels; ion channel proteins(for Na^+, K⁺, Ca²⁺, Cl^-); enzyme cascade; cAMP; acetylcholine; biogenic amines which are made from amino acids like epinephrine, norepinephrine, dopamine and serotonin; second messengers; biological responses, i.e., transport of ions, enzyme activation or deactivation, protein synthesis, and release of hormone or transmitters.

Cholinergic mechanism of transmission: A presynaptic terminal of a (motor) neuron has vesicles containing a neurotransmitter called acetylcholine(Ach). The vesicle releases Ach by exocytosis into the synaptic cleft. Ach binds at two receptor sites on a channel protein in the postsynaptic membrane and causes a change in the protein's conformation thereby opening the channel briefly for ions (Na+ or K+) to pass into or out of the postsynaptic membrane and depolarizing the membrane creating an action potential. An enzyme quickly degrades Ach into acetic acid and choline which in turn are transported back into the presynaptic terminal to be resynthesized into Ach once again. Figure 1 below shows the generalized cycle of acetycholine action and the sites in the cycle where action, synthesis or transport can be disrupted.

Figure 1. Acetylcholine pathway and sites of possible drug action at cholinergic synapses.

Biogenic amine receptor mechanism(s): Biogenic amines, i.e., epinephrine or

norepinephrine, are released as transmitters by the presynaptic terminal and attach to receptor sites on the postsynaptic membrane. This activates what are called G proteins

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which in turn activate a second messenger system involving cyclic nucleotides like cAMP. This starts a cascade of enzymatic reactions that amplify the effect of the original neuroactive agent many times over. And for this reason biogenic amine receptors (adrenergic like epinephrine and norepinephrine) tends to have a "longer lasting impact because [it] affects metabolism within the postsynaptic cell." (Campbell, 1009)

• Understand action of Cyanobacterial toxins: The specific neuronal signals between nerves and muscles can be disrupted by the toxins of Cyanobacteria causing paralysis and thus respiratory failure. The modulations by anatoxin-a, anatoxin-a(s), saxitoxin and neosaxitoxin on acetylcholine are the culprits. See Figure 2. The very real concern is that there are no FDA guidelines for the safe marketing of Cyanobacteria like Spirulina. Spirulina is being marketed as a health food and in and of itself it may not be harmful. However, the product may be contaminated by other poisonous cyanobacteria or the toxins themselves.* Check your local refrigerated juice shelves for bottles of such green "delights" as Biopower or Green Goddess; bring samples to class.

Figure 2. Three modalities of acetylcholine disruption at neuromuscular synapses* (See "Toxins of Cyanobacteria" by Carmichael.)

• Familiarize yourself if need be with the pathways that can be interrupted or modulated by various drugs. See Figure 3. These in no way are exhaustive or complete in showing the complexities involved; it only serves as a pattern to show students the potential harm to sophisticated yet vital nerve transmitter pathways.

Figure 3. Sites of possible drug interference for adrenergic synapses.

Teacher Information

Extensions and Variations

• Once students are comfortable with the cholinergic neuromuscular pathway of acetylcholine release you could have the student teams develop a possible model for drug interaction at just one specific neurological site in the context of a mini research activity. Have each team research a different drug or poison (or toxin). See appendix on Drugs of Abuse for ideas.

• Students can produce a short multi-media presentation (hyperstudio or some other computer presentation format) that captures a generalized process for modulation of the normal process by a drug at some known site in the brain and the major harms and behavioral changes due to abuse of that drug. Note: Usually drug modulations are very complex, affecting several pathways; however, have them focus on a generalized piece of the bigger picture. Describing even just one interruption will help make drug addiction and personal harm real for them.

• Use the article "Brain By Design" to open a class discussion on the bioethics and medical and social consequences of taking drugs (even supposedly therapeutic ones), of designing drugs to purposely alter neuronal activity and, therefore the bioethics, of designing one's personality.

• Use the video disc tutorial about the giant squid axon as review or Explorations in Human Biology, #9, "Synapse Action," on the CD-ROM menu.

Resources

• *"The Toxins of Cyanobacteria". Wayne W. Carmichael in Scientific American, vol. 270, pages 78-84, January 1994.

• "The Nervous System". Neil A Campbell. Biology, 4th Ed. The Benjamin/Cummings Publishing Company, Inc. 1996. Chapter 44.

• Explorations in Human Biology". George B. Johnson. Wm. C. Brown Publishers, 1995. See CD-ROM menu items #8-10.

• AXOVACS Version 1.0, written by Stephen Jones. Axon Instruments, Inc. copyright

December 1987. The current address of the company is: Axon Instruments, Inc., 1101

Chess Drive, Foster City, CA 94404-1102. (phone 415-571-9400) (email:

sales@axonet.com). This is a great package that allows neuronal views and work on a

giant squid axon.

• The Biochemical Basis of Neuropharmacology, 6th Ed. Jack R. Cooper, Floyd E. Bloom, Robert H. Roth. Oxford University Press, Inc., 1991. This is an excellent, readable text.

• Web sites:

http://web.bu.edu/COHIS/subsabse/subsabse.htm*

COHIS:Alcohol and Substance Abuse

(See the "Alcohol and Substance Abuse Menu" for information about specific drugs,

including their mechanism of action and side effects.

http://www.unl.edu/tcweb/pharm/drugs/

Index of drugs acting on the Nervous System.

http://www.sccoe.k12.ca.us/drugal.htm

Drugs, Alcohol and Tobacco Abuse - At Risk Youth Bibliography

http://www.ccsa.ca/e-lan/elanmain.htm

E-LAN is a web page created by youth, for youth to help reduce the harm associated

with drugs. Its main purpose is to present information on substance abuse and related

issues from a youth perspective. The information here is mainly for youth and youth

groups, but those that work with youth may also find it useful.

http:/www.ushc.com/health/9098.html*

US Healthcare provides a homepage called the Health Talk. This particular site is on

Depression.

About The Author

Margaret Russell is a biology/environmental science teacher at Fort Vancouver High School, 5700

East 18th St., Vancouver, Washington 98661. She can be contacted at 360-696-7111.

Student Activity

NAME OF GROUP_____________________________________DATE:______PERIOD:______

The Drug Connection: Design-O-Synapse

Bulletin from the World Health Organization (WHO)

To: WHO pharmacological units New York, San Francisco, Seattle, Wash.DC

Re: Urgent wire from Bangladesh arrived 0400

-environmentally caused deaths

Action Required: Report findings to UN HQ asap. Include educational component. Prepare team to depart for Bangladesh 0830

2 days hence

Enclosures: (See wire below.)

54 PEOPLE DEAD IN BANGLEDESH stop 364 AGRICULTURAL ANIMALS DEAD stop ASPHYXIATION stop WATER CONTAMINANT SUSPECTED STOP FIRST FLOODS AFTER DRY SPELL stop SIMILAR REPORTS COMING IN NOW FROM NEIGHBORING COUNTRIES stop SAMPLES SENT TO NY stop SITUATION URGENT stop PLEASE ADVISE stop SENDING HOURLY REPORTS DIRECTLY TO UN HEADQUARTERS stop REQUEST IMMEDIATE MEDICAL AND EDUCATIONAL SUPPORT stop

******************************************************************************

PROCEDURE:

A. You are a pharmacological unit of the World Health Organization. Assign appropriate

roles to your team members.

B. Review the wire received from Bangladesh.

C. Working cooperatively, your job is to figure out how and why the deaths are occurring

using Problem Solving Strategies.

D. You will turn in 3 components:

1. A detailed account and mind map of how your team went about solving the

problem-

a. What did you know at the start?

b. How did you narrow the problem?

c. What predictions did you make?

d. What questions needed to be asked?

e. What categories of information did you need?

f. What sub-areas in each category needed to be researched?

g. How did approach these?

h. What tasks needed to be done?

i. How was it decided who would do which tasks and when?

j. What tools and resources did you need?

k. How did you evaluate your conclusions and solution to the problem?

l. What projections could you make for further investigation?

2. A well-written detailed report to the head of the WHO (You will need to find out

who that is and the address.) advising medical and educational actions to be

taken

3. An educational component (model) that you can present. This model needs to be

very visual in order to reach masses of people in a multicultural community

-can be 3-D, creative, and/or multimedia.

E. Be ready to present to the UN subcommittee in 2 days.

See hard copy for "Drugs of Abuse" to be put in as an appendix. (3 pages)

The Woodrow Wilson National Fellowship Foundation webmaster@woodrow.org
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